Nuclear medicine and biology · 2026
Comparative biological evaluation of [18F]fluciclovine, [18F]FBPA-Fr, and [18F]FET for boron neutron capture therapy: Preclinical validation and clinical feasibility.
СтатьяСравнительное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Chang Ting-Yu, Lin Ko-Han, Lee Tzu-Yu, Tsai Yi-Ting, Chen Yi-Wei, Wu Cheng-Lin, Wu Chun-Yi
Аннотация
PURPOSE: The PET tracer 4‑borono-2-[18F]-fluoro-phenylalanine fructose ([18F]FBPA-Fr) is commonly used to estimate the biodistribution of L-4-dihydroxy-borylphenylalanine fructose (BPA-Fr). However, its limited regulatory approval has prompted the exploration of alternative imaging agents. In this study, we evaluated the feasibility of [18F]fluciclovine and [18F]fluoroethyl-tyrosine ([18F]FET) PET for pre-BNCT assessment, with direct comparison to [18F]FBPA-Fr.
METHODS: In vitro cellular uptake studies were performed using two different cancer cell lines. In vivo microPET/MR imaging and biodistribution analyses were conducted in mice bearing wild-type and L-type amino acid transporter 1 (LAT1)-knockdown GBM8401 tumors. The therapeutic efficacy of BPA-Fr-based BNCT was evaluated in tumor-bearing mice. In addition, a pilot clinical study compared [18F]fluciclovine and [18F]FBPA-Fr PET imaging in participants with brain and head-and-neck tumors.
RESULTS: [18F]FBPA-Fr uptake was strongly dependent on LAT1 expression, decreasing by approximately 60 % in LAT1-knockdown cells, whereas [18F]fluciclovine uptake was reduced by only ~10 %. In vivo, [18F]FET showed the highest absolute tumor uptake but the lowest tumor-to-normal brain (T/N) ratio due to high background activity. Mice with high [18F]fluciclovine tumor uptake exhibited significantly prolonged survival following BNCT (15-17 days) compared with controls (~10 days). Clinically, [18F]fluciclovine and [18F]FBPA-Fr showed comparable T/N ratios in patients with pontine glioma and maxillary sinus carcinoma. Moreover, [18F]fluciclovine PET visualized metabolic changes after BNCT, which were consistent with subsequent disease progression.
CONCLUSION: Although [18F]FBPA-Fr remains the most LAT1-specific tracer, [18F]fluciclovine provides comparable tumor-to-normal tissue contrast and reliable imaging performance, supporting its role as a clinically feasible alternative for pre-BNCT patient selection and treatment response assessment.
METHODS: In vitro cellular uptake studies were performed using two different cancer cell lines. In vivo microPET/MR imaging and biodistribution analyses were conducted in mice bearing wild-type and L-type amino acid transporter 1 (LAT1)-knockdown GBM8401 tumors. The therapeutic efficacy of BPA-Fr-based BNCT was evaluated in tumor-bearing mice. In addition, a pilot clinical study compared [18F]fluciclovine and [18F]FBPA-Fr PET imaging in participants with brain and head-and-neck tumors.
RESULTS: [18F]FBPA-Fr uptake was strongly dependent on LAT1 expression, decreasing by approximately 60 % in LAT1-knockdown cells, whereas [18F]fluciclovine uptake was reduced by only ~10 %. In vivo, [18F]FET showed the highest absolute tumor uptake but the lowest tumor-to-normal brain (T/N) ratio due to high background activity. Mice with high [18F]fluciclovine tumor uptake exhibited significantly prolonged survival following BNCT (15-17 days) compared with controls (~10 days). Clinically, [18F]fluciclovine and [18F]FBPA-Fr showed comparable T/N ratios in patients with pontine glioma and maxillary sinus carcinoma. Moreover, [18F]fluciclovine PET visualized metabolic changes after BNCT, which were consistent with subsequent disease progression.
CONCLUSION: Although [18F]FBPA-Fr remains the most LAT1-specific tracer, [18F]fluciclovine provides comparable tumor-to-normal tissue contrast and reliable imaging performance, supporting its role as a clinically feasible alternative for pre-BNCT patient selection and treatment response assessment.